Rotator cuff tendinopathy (RCT) is a significant source of disability and loss of work. Platelet-rich plasma (PRP) has been suggested to be beneficial in the treatment of RCT. To investigate the effect of PRP injections on pain and shoulder functions in patients with chronic RCT. Randomized controlled trial; Level of evidence, 1. A total of 40 patients, 18 to 70 years of age, with (1) a history of shoulder pain for >3 months during overhead-throwing activities, (2) MRI findings of RCT or partial tendon ruptures, and (3) a minimum 50% reduction in shoulder pain with subacromial injections of an anesthetic were included in this placebo-controlled, double-blind randomized clinical trial. Patients were randomized into a PRP group (n = 20) or placebo group (n = 20). Patients received an ultrasound-guided injection into the subacromial space that contained either 5 mL of PRP prepared from autologous venous blood or 5 mL of saline solution. All patients underwent a 6-week standard exercise program. Outcome measures (Western Ontario Rotator Cuff Index [WORC], Shoulder Pain and Disability Index [SPADI], 100-mm visual analog scale [VAS] of shoulder pain with the Neer test, and shoulder range of motion) were assessed at baseline and at 3, 6, 12, and 24 weeks and 1 year after injection. Comparison of the patients revealed no significant difference between the groups in WORC, SPADI, and VAS scores at 1-year follow-up (P = .174, P = .314, and P = .904, respectively). Similar results were found at other assessment points. Within each group, the WORC, SPADI, and VAS scores showed significant improvements compared with baseline at all time points (P < .001). In the range of motion measures, there were no significant group × time interactions. At 1-year follow-up, a PRP injection was found to be no more effective in improving quality of life, pain, disability, and shoulder range of motion than placebo in patients with chronic RCT who were treated with an exercise program.